A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Understanding the Immune System and Biospecimen-Based Response in Glioblastoma: A Practical Guide to Utilizing Signal Redundancy for Biomarker and Immune Signature Discovery.

Glioblastoma (GBM) is a primary central nervous system malignancy with a median survival of 15-20 months. The presence of both intra- and intertumoral heterogeneity limits understanding of biological mechanisms leading to tumor resistance, including immune escape. An attractive field of research to examine treatment resistance are immune signatures composed of cluster of differentiation (CD) markers and cytokines.

Mucins as Precision Biomarkers in Glioma: Emerging Evidence for Their Potential in Biospecimen Analysis and Outcome Prediction.

Despite attempts at improving survival by employing novel therapies, progression in glioma is nearly universal. Precision biomarkers are critical to advancing outcomes; however, biomarkers for glioma are currently unknown. Most data on which the field can draw for biomarker identification comprise tissue-based analysis requiring the biospecimen to be removed from the tumor.

The pseudoknot structure of a viral RNA reveals a conserved mechanism for programmed exoribonuclease resistance.

Exoribonuclease-resistant RNAs (xrRNAs) are viral RNA structures that block degradation by cellular 5'-3' exoribonucleases to produce subgenomic viral RNAs during infection. Initially discovered in flaviviruses, xrRNAs have since been identified in wide range of RNA viruses, including those that infect plants. High sequence variability among viral xrRNAs raises questions about the shared molecular features that characterize this functional RNA class.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).